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991.
The synthesis of 14C‐labeled, 13CD2‐labeled saxagliptin,and its 13CD2‐labeled 5‐hydroxy metabolite 下载免费PDF全文
Scott B. Tran Brad D. Maxwell Kai Cao Samuel J. Bonacorsi 《Journal of labelled compounds & radiopharmaceuticals》2014,57(3):136-140
14C‐labeled saxagliptin, 13CD2‐labeled saxagliptin, and its 13CD2‐labeled 5‐hydroxy metabolite were synthesized to further support development of the compound for biological studies. This paper describes new syntheses leading to the desired compounds. A total of 3.0 mCi of 14C‐labeled saxagliptin was obtained with a specific activity of 53.98 μCi/mg (17.13 mCi/mmol). The radiochemical purity determined by HPLC was 99.29%, and the overall radiochemical yield was 3.0% based upon 100 mCi of [14C]CH2I2 starting material. By following similar synthetic routes, 580.0 mg of 13CD2‐labeled saxagliptin and 153.1 mg of 13CD2‐labeled 5‐hydroxysaxagliptin metabolite were prepared. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Preclinical studies have implicated noradrenergic (NA) dysfunction in cocaine addiction. In particular, the NA system plays a central role in motivated behavior and may partake in the regulation of craving and drug use. Yet, human studies of the NA system are scarce, likely hampered by the difficulty in precisely localizing the locus coeruleus (LC). Here, we used neuromelanin imaging to localize the LC and quantified LC neuromelanin signal (NMS) intensity in 44 current cocaine users (CU; 37 men) and 59 nondrug users (NU; 44 men). We also employed fMRI to investigate cue-induced regional responses and LC functional connectivities, as quantified by generalized psychophysiological interaction (gPPI), in CU. Imaging data were processed by published routines and the findings were evaluated with a corrected threshold. We examined how these neural measures were associated with chronic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ). Compared to NU, CU demonstrated higher LC NMS for all probabilistic thresholds defined of 50–90% of the peak. In contrast, NMS of the ventral tegmental area/substantia nigra (VTA/SN) did not show significant group differences. Drug as compared to neutral cues elicited higher activations of many cortical and subcortical regions, none of which were significantly correlated with CCQ score. Drug vs. neutral cues also elicited “deactivation” of bilateral parahippocampal gyri (PHG) and PHG gPPI with a wide array of cortical and subcortical regions, including the ventral striatum and, with small volume correction, the LC. Less deactivation of the PHG (r = 0.40, p = 0.008) and higher PHG-LC gPPI (r = 0.44, p = 0.003) were positively correlated with the CCQ score. In contrast, PHG-VTA/SN connectivity did not correlate with the CCQ score. Together, chronic cocaine exposure may induce higher NMS intensity, suggesting neurotoxic effects on the LC. The correlation of cue-elicited PHG LC connectivity with CCQ score suggests a noradrenergic correlate of chronic cocaine craving. Potentially compensating for memory functions as in neurodegenerative conditions, cue-elicited PHG LC circuit connectivity plays an ill-adaptive role in supporting cocaine craving.Subject terms: Predictive markers, Motivation 相似文献
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Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes 下载免费PDF全文
Honglei Wang Zhenzhen Wang Parimi Leela Rani Xi'an Fu Wenjun Yu Fangfang Bao Gongqi Yu Jianke Li Lulu Li Lele Sun Zhenhua Yue Qing Zhao Qing Pan Jing Cao Chuan Wang Xiaojun Chi Yaru Wang Qing Yang Zihao Mi Hong Liu Furen Zhang 《Experimental dermatology》2017,26(11):1112-1117
The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10?5, OR=5.07), rs16861329 on 3q27.3 (P=2.02×10?4, OR=0.87) and rs849135 on 7p15.1 (P=6.59×10?9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T‐cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes. 相似文献
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目的:观察桔梗配伍对人乳腺癌高肺转移细胞株MDA231-LM2增殖及侵袭的干预作用,并围绕"自激注入"现象从IL-6、IL-8、MMP1、CXCL1角度,探讨其作用机制。方法:采用MTT法及Transwell法观察桔梗配伍即养阴润肺组(桔梗配伍麦冬含药血清)、活血散结组(桔梗配伍莪术含药血清)对MDA231-LM2细胞增殖及侵袭作用的影响;实时荧光定量PCR法检测桔梗配伍两组对MDA231-LM2细胞IL-6、IL-8、MMP1、CXCL1基因表达的影响;ELISA法检测桔梗配伍两组对MDA231-LM2细胞IL-6、IL-8、MMP1、CXCL1蛋白表达的影响。结果:1桔梗配伍对乳腺癌肺转移有不同程度抑制作用;2与对照组比较,养阴润肺组、活血散结组IL-6、IL-8、CXCL1的mRNA及蛋白表达量明显升高,MMP1的mRNA及蛋白表达量明显降低(P0.05,P0.01)。结论:桔梗配伍对人乳腺癌高肺转移细胞株MDA231-LM2增殖及侵袭有抑制作用,其作用机制可能与调节IL-6、IL-8、MMP1、CXCL1的表达有关。 相似文献
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Q. Shen Y. Chen S. Gokavarapu W. Cao T. Ji 《The British journal of oral & maxillofacial surgery》2018,56(1):48-53
To establish the prognostic factors for primary intraosseous squamous cell carcinoma we designed a retrospective study of patients treated in the head and neck department of a tertiary referral centre in China from 2010–2015. We collected clinical, radiological, and histopathological data from 36 patients treated during the given time period, among which 34 were followed up. There were 22 male and 12 female patients, 13 of whom gave a history of smoking tobacco and four who drank alcohol. All 34 patients were treated by segmental mandibulectomy and neck dissection. Nine had cervical lymph node metastases on histopathological examination, and none had invaded surgical margins. Twenty-eight were treated with radiotherapy postoperatively. During follow up nine died of locoregional recurrence or metastases. Specific factors such as cervical lymph node metastases were related to a greater likelihood of locoregional recurrence. Patients who drank alcohol were also more likely to develop metastases postoperatively. Tumours more than 4 cm in size were significantly associated with reductions in locoregional control and survival. 相似文献
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